Multiple sclerosis may be an autoimmune disease and chronic relapsing experimental allergic encephalomyelitis (CR-EAE) is the best animal model for this illness. Recognition of major histocompatibility complex (MHC) antigens on organs such as brain may be important in the development of autoimmune responses to such organs. We propose to investigate the role of brain MHC antigens in the development of CR-EAE by: a) determining the presence and ease of modulation of these antigens on brains cells from the CR-EAE susceptible strain of mice; b) investigating whether recognition of MHC antigens on glial cells is required for the development of CR-EAE; c) investigating whether immune reactions in brain can induce recognition of MHC antigens on brain cells and thus increase susceptibility to CR-EAE. We propose to use a combination of in vivo and in vitro techniques to answer these questions and obtain a clearer understanding of those factors responsible for the initiation of autoimmune phenomena.